One characteristic which distingishes sarcoidosis from other similar granulomatous diseases such as tuberculosis is the induction of angiotensin converting enzyme (ACE) in th granuloma epithelioid cells and the corresponding increase in serum ACE activity. It is currently thought that the increased serum ACE in sarcoidosis is derived from the granuloma epithelioid cells. Although the mechanism of ACE induction in the sarcoid epithelioid cells is not known, it is likely that T-lymphocytes at the granuloma site are involved given their critical role in granuloma maintenance. We have confirmed the observations that human peripheralblood monocytes from both normal subjects and sarcoidosis patients are induced to synthesize ACE when cultured on plastic and that autologous peripheral blood lymphocytes from normal subjects but not from sarcoidosis patients can also induce ACE in monocytes. Since monocytes are the presumed precursor cells of the sarcoid granuloma epithelioid cell, we propose to investigate the mechanism of ACE induction in cultured monocytes from both normal subjects and sarcoidosis patients. For sarcoidosis patients, we will also examine the ability of T-lymphocytes obtained from bronchoalveolar lavage to induce ACE. These lymphocytes should represent as in vivo activated set of lymphocytes. T-lymphocytes from both normal subjects and sarcoidosis patients will be fractionated by a variety of techniques to determine if a specific subpopulation is responsible for ACE induction. The characteristics of ACE induction due to adherence will be determined and compared to those due to T-lymphocyte mediated induction. Among the characteristics examined will be time dependence and magnitude of induction. These studies will also examine the induction of monocyte proteins in general. The properties of the induced ACE will be determined and compared to the physio-chemical and kinetic properties of purified human pulmonary endothelial ACE. In addition, we will attempt to confirm the observation that a lymphokine generated in monocyte-lymphocyte co-cultures can also induce ACE in monocytes. The properties and cellular source of this lymphokine will be investigated and its mechanism of induction compared to that due to adherence and due to T-lynphocytes. The induction of ACE is cultured human monocytes should be a useful model for the induction of ACE in sarcoidosis and could lead to new insights into the pathogenesis of sarcoidosis.